Across the world, transboundary water pollution interferes with man's use of water, degrades aquatic ecosystems, causes human health impacts, and increases tensions between nations. While developing nations are just beginning to assess the extent of transboundary water quality degradation, developed countries have learned over the years that pollution prevention, not cleanup actions or end-of-pipe treatment is the most cost-effective approach to fighting water pollution. The extent of transboundary water pollution across the world is reviewed in the paper, and key elements are outlined for addressing pollution prevention needs through joint institutions as part of international commissions. The Great Lakes/St. Lawrence River basin in North America is used as an example of where multimedia pollution prevention initiatives are being implemented to resolve transboundary pollution problems. The joint institutions for the Great Lakes cleanup utilized under the auspices of the International Joint Commission (U.S. and Canada) are described. Lessons learned from this experience include: (1) significance of multimedia pollution prevention measures to address toxic substances, (2) use of ecosystem-based, watershed approaches targeted to high priority catchments, and (3) political advantages of employing joint institutions to facilitate progress, undertake oversight and verification functions, foster public participation, and establish credibility and trust among the parties through joint fact-finding.